The principal objective of this project is to apply state-of-the-art gas chromatographic/mass spectrometric methodologies to the analysis of trace levels of fatty acid metabolites in an effort to elucidate the molecular alterations involved in various neuropathological states. These compounds are generally potent agents that are present in extremely low levels as part of a complex mixture and, therefore, other techniques often are unable to provide useful results. During the first phase of this research, emphasis has been placed on characterizing the levels of prostaglandins in human cerebrospinal fluid (CSF). Extensive investigations regarding the preparation of samples for GC/MS analysis have resulted in several methodological modifications, providing an improvement in sample recovery and the limits of detection. Cerebrospinal fluid samples from various patient classes have been analyzed; prostaglandins PGF-1a PGF-2a, and 6-keto-PGF-1a were quantifiable in the samples, while levels of PGE-2 and PGE-2 were usually below detection limits. Studies aimed at further improvements in detection limits and methods development for analysis of other prostaglandins are in progress.